HMG-CoA reductase has been shown to be the major control enzyme for hepatic cholesterol biosynthesis. In view of the probable causal relationship between cholesterol and atherosclerosis, HMG-CoA reductase has obvious significance. Despite the importance of this enzyme, it has not been completely purified and characterized. We have developed a simple and reliable means of solubilizing the reductase from rat liver microsomes without the use of detergents or organic solvents. We have partly purified the enzyme and determined some of its properties. We propose to complete the purification and characterization. We propose to determine the effect of possible natural and synthetic inhibitors on both the soluble and particle bound HMG-CoA reductase. Finally, we propose to solubilize and purify the enzyme from human liver.